Diffuse Large B-Cell Lymphoma (DLBCL) is the most common form of lymphoma, comprising nearly 30% of all lymphoma cases. DLBCL is both clinically and molecularly heterogeneous. While nearly half of the patients are cured with standard therapy, the majority of the remaining patients succumb to the disease. In this proposal, we develop several complementary approaches that allow us to connect the specific genetic mutations in lymphomas to their context-specific roles. We propose to define the association of individual alterations with outcome, while accounting for the genetic heterogeneity among tumors. We have previously identified GNA13 as a commonly mutated gene in germinal center derived lymphomas including a subset of DLBCLs. We further propose to define lymphoma-specific roles of GNA13, as well as other variants that will be identified with this larger sample cohort through in vitro and in vivo approaches.